The preparation of microparticles is mainly used so as to delay the dissolution of active principles and, because of this, finds numerous applications in the field of controlled-release medicaments and in the field of masking the taste of medicaments intended for oral administration. However, it has always been difficult to develop a formulation containing microparticles in the form of unit doses and in particular a formulation suitable for oral administration.
In fact, the industrial preparation of tablets and capsules requires free-flowing and/or cohesion properties of the granule to be subdivided, which the microparticles do not necessarily possess.
The tablet presents problems of the integrity of the microparticles under the effect of the compression; its slow rate of disintegration does not always allow it to be administered after disintegration and suspending in a glass of water.
The capsule does not always allow the dispersion of the particles in the gastrointestinal tract.
Moreover, both the capsule and the tablet present problems in swallowing, which are particularly pronounced in children and old people.
Finally, the sachet is an expensive pharmaceutical form, for non-ambulant use and the dry syrup form can frequently not be produced for reasons of early liberation of the active principle out of the microparticles or physical and/or chemical stability of the preparation.
The production of beads, better known in the prior art under the term prills, is described in the patents European Patent No. 277,508, U.S. Pat. Nos. 4,525,198 and 4,389,356. Unfortunately, the processes for the preparation of these beads are not applicable to all products.
These processes are used for products which can be subjected to sudden heating intended to render them molten and to rapid cooling to ensure their solidification. On the other hand, they are of poor suitability for the pharmaceutical industry which uses regular bead sizes of the order of a few tens to a few hundred microns are desired.
French Patents 2 036 890 and 2 366 835 describe pharmaceutical forms having the characteristic of rapidly dissolving or disintegrating in an aqueous medium or in the saliva.
It has now been found that techniques having totally opposed aims, such as delaying the dissolution of an active principle on the one hand and the fact that the pharmaceutical form rapidly disintegrates or dissolves on the other hand, can be combined in such a way as to obtain a lyophilized single dosage form, which is able to disintegrate easily and rapidly in water, which contains the active principle in the form of beads and in which settling and/or rising to the surface of the particles during lyophilization has been prevented.